A Phase II Study Evaluating the Safety and Efficacy of Subcutaneous Plerixafor

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase II Study Evaluating the Safety and Efficacy of Subcutaneous Plerixafor for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Recipients With Hematological Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01696461
• Other study ID #: 09-PLEX
• Status: Completed
• Phase: Phase 2
• Start date: May 2013
• Est. completion date: August 2016

Study information

• Verified date: May 2023
• Source: Center for International Blood and Marrow Transplant Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II, open-label, two strata, multicenter, prospective study of plerixafor-mobilized HLA-identical sibling allografts in recipients with hematological malignancies. This study will establish the safety and efficacy of subcutaneous plerixafor for this purpose.

Description:

The primary objective is to determine the proportion of donors whose cells can be successfully mobilized and collected with a sufficient CD34+ cell dose using plerixafor as the mobilizing agent, using an intention-to-treat analysis. Donor mobilization following plerixafor will be considered successful if ≥ 2.0x10e6 CD34+ cells/kg recipient weight are collected in no more than two leukapheresis collections.

All donors receiving plerixafor will be included in the analysis of the primary objective based on the intention-to-treat principle.Recipients will be classified into one of the two strata, myeloablative or reduced intensity, according to his/her conditioning regimen. The target enrollment is 64 donor/recipient pairs, 32 pairs per stratum.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Donor:

• Donor eligibility will be determined according to applicable federal, state and local regulations and institutional standards

• 18-65 years of age

• 6/6 HLA-matched sibling

• Fulfill individual Transplant Center criteria to serve as a mobilized blood cell donor

• Serum creatinine <2.0mg/dl

Recipient:

• 18 to 65 years of age

• 6/6 HLA antigen matched sibling willing to donate PBSC for transplant

• Fulfill individual Transplant Center Criteria for transplant

• One of the following diagnoses:

• Acute myelogenous leukemia (AML) in 1st remission or beyond with <5% marrow blasts and no circulating blasts. Marrow must be done within 30 days of the start of transplant conditioning regimen in alignment with other pre-transplant assessments.

• Acute lymphoblastic leukemia (ALL) in 1st remission or beyond with <5% marrow blasts and no circulating blasts

• Myelodysplastic syndrome, either intermediate-1,2, or high risk by International Prognostic Scoring System or transfusion dependent

• Chronic myelogenous leukemia (CML) failing or intolerant to tyrosine kinase inhibitor based therapy

• Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or in relapse (but with at least stable disease after most recent therapy)

• Chronic lymphocytic leukemia (CLL), relapsing after at least one prior regimen, or in remission with 17p deletion

• Serum creatinine must be <2.0mg/dl

• Total bilirubin and aspartate aminotransferase (AST) <3x normal

• Infectious disease marker (IDM) monitoring will be performed per institutional standards

• Karnofsky performance status of 70% or greater.

• Patients who have undergone a prior autologous transplantation are eligible for a reduced intensity transplant only

Exclusion Criteria:

Donor:

• Donor unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing

• Donor already enrolled on another investigational agent study

• Pregnant or breast feeding females, or females not willing or able to use adequate contraception if sexually active

Recipient:

• Patient unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing

• Patients with active, uncontrolled infection at the time of the transplant preparative regimen

• Pregnant or breast feeding females, or females not willing or able to use adequate contraception if sexually active

• Patients with a history of previous central nervous system (CNS) tumor involvement showing active symptoms or signs along with documented disease on lumbar puncture and MRI of the brain within 30 days of start of conditioning

• A condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of primary and secondary endpoints.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myelogenous Leukemia
• Chronic Lymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Hodgkin Disease
• Hodgkin's Disease
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Non-Hodgkin's Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Plerixafor

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Duke University	Durham	North Carolina
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Center for International Blood and Marrow Transplant Research	Genzyme, a Sanofi Company, Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Donors Whose Cells Were Successfully Mobilized and Collected With a Sufficient CD34+ Cell Dose Using Plerixafor as the Mobilizing Agent, Using an Intention-to-treat Analysis.	Donor mobilization following plerixafor was considered successful if = 2.0x106 CD34+ cells/kg recipient weight was collected in no more than two leukapheresis collections.	donation
Secondary	Incidence and Severity of Acute Toxicities	Incidence and severity of acute toxicities before and during apheresis experienced by donors receiving plerixafor. Acute toxicities are graded according to the NCI Common Terminology Criteria for Adverse Events, version 4.0. This outcome measure is descriptive. Grade of maximum toxicity across all time points is reported. Higher grades denote worse outcomes. 0 = None, 1 = Mild, 2 = Moderate, 3 = severe.	baseline, Day 1, Day 2, Day 3
Secondary	Adverse Effects	Adverse effects experienced by donors receiving plerixafor up to one year post donation. Number of participants with a maximum MTC >0 reported at each individual time point. Adverse effects are graded according to the NCI Common Terminology Criteria for Adverse Events, version 4.0. This outcome measure is descriptive. Participants can experience adverse effects at more than one time point evaluated. Higher grades denote worse outcomes. 0 = None, 1 = Mild, 2 = Moderate, 3 = severe.	30 minutes, 60 minutes, 120 minutes, 240 minutes, 1 month, 6 months, 12 months post donation for each subject
Secondary	Incidence of and Kinetics of Neutrophil and Platelet Recovery After Transplantation of Hematopoietic Cells Mobilized With Plerixafor	Incidence of and kinetics of neutrophil and platelet recovery by day 100 in recipients after transplantation of hematopoietic cells mobilized with plerixafor.	Day +1 through neutrophil recovery or Day 21 (whichever is first)
Secondary	T-cell (CD3+) and Myeloid (CD33+) Chimerism After Transplantation of Hematopoietic Cells Mobilized With Plerixafor	T-cell (CD3+) and myeloid (CD33+) chimerism in recipients after transplantation of hematopoietic cells mobilized with plerixafor. This outcome measure is descriptive.	Chimerism was evaluated at serial timepoints post HCT in patients in both RIC and MAC strata. Chimerism was assessed at Day +28, +100, +180, and +365
Secondary	Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With Plerixafor	Incidence of primary graft failure in recipients after transplantation of hematopoietic cells mobilized with plerixafor. This outcome measure is descriptive.	Day 28
Secondary	Incidence of Acute Graft-versus-host Disease (GVHD)	Incidence of acute graft-versus-host disease (GVHD) in recipients after transplantation of hematopoietic cells mobilized with plerixafor	Day 100
Secondary	Immune Reconstitution	Rate and quality of immune reconstitution as evidenced by peripheral blood immunophenotype after transplantation of hematopoietic cells mobilized with plerixafor.	Day 28, 100, 180, 365
Secondary	Incidence of Cytomegalovirus (CMV) Reactivation After Transplantation With Cells Mobilized With Plerixafor.	Percentage of recipients with prior CMV infection whose CMV was reactivated after transplantation with cell mobilized with plerixafor	day 365
Secondary	Treatment-related Mortality and Disease Relapse/Progression	Incidence of treatment-related mortality and disease relapse/progression in recipients after transplantation of hematopoietic cells mobilized with plerixafor	Day 180, 365
Secondary	Progression-free and Overall Survival	Probability of progression-free and overall survival after transplantation of hematopoietic cells mobilized with plerixafor	Day 180, 365
Secondary	Cellular Composition of Allografts	Cellular composition of allografts mobilized with plerixafor (stem/progenitor cells, T/B/ (Natural killer) NK-cells)	donation
Secondary	Incidence of Chronic Graft-versus-host Disease (GVHD)	Incidence of chronic graft-versus-host disease (GVHD) in recipients after transplantation of hematopoietic cells mobilized with plerixafor	Day 365
Secondary	Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With Plerixafor	Incidence of secondary graft failure in recipients after transplantation of hematopoietic cells mobilized with plerixafor. This outcome measure is descriptive.	Day 365
Secondary	CD34+ Cell Count of Allografts	CD34+ cell count of allografts mobilized with plerixafor	donation